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Solid Tumor, AdultPhase 1/2NCT04474470

A Study to Evaluate NT219 Alone and in Combination with ERBITUX® (Cetuximab) in Adults with Advanced Solid Tumors and Head and Neck Cancer

A Phase 1/2 study testing NT219, NT219 and ERBITUX® - Dose Escalation and NT219 and ERBITUX® - Expansion in people with Solid Tumor, Adult and Squamous Cell Carcinoma of Head and Neck, run by TyrNovo Ltd. at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase 1/2, multi-center study with an open-label, dose escalation phase followed by a single-arm expansion phase to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 alone and in combination with ERBITUX® (cetuximab) in adults with recurrent and/or metastatic solid… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
NT219, NT219 and ERBITUX® - Dose Escalation and NT219 and ERBITUX® - Expansion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
10 sitesin 2 countries
Study dates
3 Sep 2020to 8 May 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • The exclusion criteria for Study Portion #2 drug combination dose escalation and Study Portion#3, the expansion phases of the trial are identical. Subjects meeting any of the following exclusion criteria will not be enrolled in the trial:
  • Nasal, paranasal sinus, or nasopharyngeal carcinoma and mutated KRAS colorectal adenocarcinoma, aside from World Health Organization (WHO) Type I and II [keratinizing, non-Epstein-Barr virus (EBV) positive] nasopharyngeal carcinoma which will be allowed;
  • In Study Part 2: For subjects with HNSCC: Received more than 2 prior systemic regimens for their HNSCC; For subjects with CRC: Received more than 3 prior systemic regimens for their CRC; In Study Part 3: For subjects with HNSCC: Received more than 2 prior regimens for their recurrent/metastatic HNSCC
  • Received cetuximab as part of the most recent regimen and/or within the last 6 months prior to study registration
  • Any invasive cancer (other than non-melanoma skin cancer) different from the current disease within 3 years of Screening
  • Known hypersensitivity to ERBITUX® or other epidermal growth factor receptor (EGFR), Janus kinase (JAK), or signal transducer and activator of transcription (STAT) antagonists/inhibitors, or inactive ingredients of NT219 Injection.
Show all 32Show fewer
  • Radiation or major surgery within 4 weeks prior to the first dose of NT219;
  • Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer
  • Parenteral vitamin C administration and oral supplements containing vitamin C
  • History of weight loss >10% over the 2 months prior to Screening
  • Active, untreated central nervous system (CNS) metastases
  • Severely immunocompromised as defined by white blood cell (WBC) count <2000/mm3 and/or CD4+ lymphocyte count ≤200/mm3
  • Major surgery within 4 weeks of study administration;
  • Known allergy to tick bites or red meat, or known immunoglobulin E (IgE) antibodies directed against galactose-α-1,3-galactose
  • Any condition which, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study
  • Clinically relevant serious co-morbid medical conditions including, but not limited to:
  • Active infection
  • History of long QT syndrome or corrected QT interval (QTc) or QT/QTc interval measured as prolonged at screening (>480 ms; using Fredericia's QT correction formula). Note: subjects who screen fail due to this criterion are not eligible to be re-screened;
  • A history of additional risk factors for TdP including clinically significant prolonged electrolytes imbalance, left ventricular dysfunction and left ventricular hypertrophy, prolonged diarrhea, bradycardia < 60 bpm, past history of syncope or a family history of sudden death at age <40 years
  • The use of concomitant medications that prolong the QT/QTc interval or experienced arrhythmias with use of agents known to induce TdP.
  • Recent (within six months of Screening) New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, or severe or unstable angina;
  • History of serious arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications
  • Global Initiative for Chronic Obstructive Lung Disease (GOLD) score ≥3 chronic obstructive or chronic restrictive pulmonary disease, pulmonary hypertension, or interstitial pneumonitis
  • Active CNS disease including carcinomatous meningitis;
  • Psychiatric illness/social situation that would limit compliance with study requirements; Prior organ allograft
  • Subjects with active, known or suspected autoimmune disease. Subjects with the following are permitted to enroll: (subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid patients with a history of Grave's disease (subjects with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study drug), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses >10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted.
  • History of active or latent tuberculosis infection
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as follows:
  • Subjects with HIV: detectable viral load and CD4 count below 200 cells/mm3; Subjects with HBV (HepBsAg+): serum HBV DNA polymerase chain reaction (PCR) that is above the limit of detection Subjects with HCV (Ab +): detectable HCV RNA by PCR
  • Pregnant or lactating women
  • Use of UGT inhibitors within 14 days prior to first dose of study treatment. Morphine and similar agents and statins which are commonly used in oncology subjects are permitted. See Appendix E for sample list of prohibited UGT inhibitors.

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

United States7 sites

  • The University of Chicago and Biological Sciences

    Chicago, Illinois, 60637

  • California Cancer Associates for Research and Excellence

    Encinitas, California, 92024

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73117

  • UCSD Moores Cancer Center

    San Diego, California, 92037

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

Israel3 sites

  • Hadassah University Medical Center

    Jerusalem

  • Rabin Medical Center

    Petah Tikva

  • Sourasky Medical Center

    Tel Aviv

Other trials in Israel

About this study

Official title: A Phase 1/2 Study with Open-Label, Dose Escalation Phase Followed by Single-Arm Expansion At the Maximum Tolerated Dose to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of NT219 Injection Alone and in Combination with ERBITUX® (Cetuximab) in Adults with Advanced Solid Tumors and Head and Neck Cancer

This is a phase 1/2, multi-center study with an open-label, dose escalation phase followed by a single-arm expansion phase to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 alone and in combination with ERBITUX® (cetuximab) in adults with recurrent and/or metastatic solid tumors.

Being tested
NT219, NT219 and ERBITUX® - Dose Escalation, NT219 and ERBITUX® - Expansion
Keywords
NT219, ERBITUX, Cetuximab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NT219Drug

    Dose escalation of NT219 as a single agent in adult subjects with recurrent and/or metastatic solid tumors

  • NT219 and ERBITUX® - Dose EscalationDrug

    Dose escalation of NT219 in combination with standard dose ERBITUX® in adult subjects with recurrent and/or metastatic squamous cell carcinoma of the head and neck and colorectal adenocarcinoma

  • NT219 and ERBITUX® - ExpansionDrug

    Expansion cohort of NT219 at its RP2D in combination with standard dose ERBITUX® in adult patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

Study groups in NCT04474470
Study groupRoleWhat they receive
Dose escalation of NT219 as a single agentExperimentalNot described
Receives: Drug: NT219
Dose escalation of NT219 in combination with ERBITUX®ExperimentalNot described
Receives: Drug: NT219 and ERBITUX® - Dose Escalation
Expansion cohort of NT219 in combination with ERBITUX®ExperimentalNot described
Receives: Drug: NT219 and ERBITUX® - Expansion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Incidence of treatment emergent adverse events

    Incidence of treatment emergent adverse events with single agent NT219

    Measured: Up to 24 months

  2. Part 2: Incidence of treatment emergent adverse events

    Incidence of treatment emergent adverse events with NT219 administered in combination with ERBITUX®

    Measured: Up to 24 months

  3. Part 3: Objective Response Rate

    Objective Response Rate when phase 2 dose of NT219 is used in combination with ERBITUX® in adults with recurrent and/or metastatic SCCHN

    Measured: Up to 24 months

Secondary outcomes (19)

  1. Area under the plasma concentration curve [AUC]

    Area under the plasma concentration curve [AUC] of NT219

    Measured: Up to 45 days after first study drug administration

  2. Maximum plasma concentration [Cmax]

    Maximum plasma concentration [Cmax] of NT219

    Measured: Up to 45 days after first study drug administration

  3. Volume of distribution at stead-state [Vss]

    Volume of distribution at stead-state [Vss] of NT219

    Measured: Up to 45 days after first study drug administration

  4. Plasma half-life [t1/2]

    Plasma half-life [t1/2] of NT219

    Measured: Up to 45 days after first study drug administration

  5. Plasma clearance [Cl]

    Plasma clearance [Cl] of NT219

    Measured: Up to 45 days after first study drug administration

  6. Objective Response Rate when NT219 is used as monotherapy

    Measured: Up to 24 months

  7. Duration of Response when NT219 is used as monotherapy

    Measured: Up to 24 months

  8. Time to Response when NT219 is used as monotherapy

    Measured: Up to 24 months

  9. Disease Control Rate when NT219 is used as monotherapy

    Measured: Up to 24 months

  10. Progression Free Survival when NT219 is used as monotherapy

    Measured: Up to 24 months

  11. Time to Progression when NT219 is used as monotherapy

    Measured: Up to 24 months

  12. Overall Survival when NT219 is used as monotherapy

    Measured: Up to 24 months

  13. Objective Response Rate when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  14. Duration of Response when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  15. Time to Response when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  16. Disease Control Rate when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  17. Progression Free Survival when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  18. Time to Progression when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

  19. Overall Survival when NT219 is used in combination with ERBITUX®

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2020
  2. Study start3 Sep 2020
  3. Primary completion8 May 2024
  4. Study completion8 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04474470
Sponsor's protocol ID
TYR-219-01
Status last verified
May 2024
First submitted
30 Jun 2020
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NT219, NT219 and ERBITUX® - Dose Escalation and NT219 and ERBITUX® - Expansion in people with Solid Tumor, Adult and Squamous Cell Carcinoma of Head and Neck, run by TyrNovo Ltd. at 10 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Incidence of treatment emergent adverse events (time frame: Up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04474470.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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